DOCSLIB.ORG

Chronicling the Discovery of Interferon Tau

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Chronicling the Discovery of Interferon Tau REPRODUCTIONANNIVERSARY REVIEW Chronicling the discovery of interferon tau Fuller W Bazer1 and William W Thatcher2 1Department of Animal Science, Texas A&M University, College Station, Texas, USA and 2Department of Animal Science, University of Florida, Gainesville, Florida, USA Correspondence should be addressed to F W Bazer; Email: [email protected] Abstract It has been 38 years since a protein, now known as interferon tau (IFNT), was discovered in ovine conceptus-conditioned culture medium. After 1979, purification and testing of native IFNT revealed its unique antiluteolyic activity to prevent the regression of corpora lutea on ovaries of nonpregnant ewes. Antiviral, antiproliferative and immunomodulatory properties of native and recombinant IFNT were demonstrated later. In addition, progesterone and IFNT were found to act cooperatively to silence expression of classical interferon stimulated genes in a cell-specific manner in ovine uterine luminal and superficial glandular epithelia. But, IFNT signaling through a STAT1/STAT2-independent pathway stimulates expression of genes, such as those for transport of glucose and amino acids, which are required for growth and development of the conceptus. Further, undefined mechanisms of action of IFNT are key to a servomechanism that allows ovine placental lactogen and placental growth hormone to affect the development of uterine glands and their expression of genes throughout gestation. IFNT also acts systemically to induce the expression of interferon stimulated genes that influence secretion of progesterone by the corpus luteum. Finally, IFNT has great potential as a therapeutic agent due to its low cytotoxicity, anti-inflammatory properties and effects to mitigate diabetes, obesity-associated syndromes and various autoimmune diseases. Reproduction (2017) 154 F11–F20 Embryonic death, uterine factors and pregnancy both of which limited litter size at term (Bazer et al. 1968, 1969). A number of historical events set the stage for research leading to the discovery of pregnancy recognition signals in pigs and ruminant species. Bazer and coworkers Concept of pregnancy recognition signaling (1969) noted that hormone-induced superovulation and While attention was being given to embryonic death, feeding high-energy feeds, to increase the number of uterine factors and pregnancy in pigs, Short (1979) ovulations in polytocous animals, led to greater rates clarified the terms luteotrophic, luteolytic, antiluteolytic of embryonic death due to inherent limitations within and pregnancy recognition signaling. Prostaglandin F individual embryos and to maternal limitations that 2α (PGF) was identified as the uterine-derived luteolytic restrict litter size or both. Embryonic death losses occur hormone responsible for regression of the CL and during the peri-implantation period of pregnancy (Boyd cessation of secretion of progesterone by luteal cells 1965) and increase following hormonal superovulation in nonpregnant subprimate mammals (Schramm et al. (Fowler & Edwards 1957, Adams 1960, Hafez 1964) 1983). The antiluteolytic signals from pig and ruminant or the transfer of additional embryos to uterine horns conceptuses had not been identified in 1969, but it of mice (McLaren & Michie 1959, Adams 1960, Hafez was assumed that those signals inhibited luteolytic 1964). Bazer et al. (1969) postulated that a biochemical actions of PGF or abrogated the mechanism(s) for PGF- factor in the uterine lumen limited the number of induced luteolysis. Pregnancy recognition signals were blastocysts that undergo implantation and placentation. diverse (Flint et al. 1979). For example, available results This idea supported results of Krishnan and Daniel indicated the lack of need for pregnancy recognition (1967) who discovered blastokinin (also known as signals for dogs, ferrets and marsupials, but systemic uteroglobin). Blastokinin was reported to induce the effects of estrogens on functions of corpora lutea (CL) in development of morulae to blastocysts in rabbits. The pregnant pigs had been reported (Kraeling et al. 1975). fact that most embryonic deaths in pigs occur during Short (1979) reported that abnormal conceptuses failed the peri-implantation period of pregnancy (Gossett & to signal pregnancy recognition. Thus, the stage was set Sorensen 1959) suggested that the major causes were for research to identify pregnancy recognition signals failure of blastocysts to develop and/or uterine capacity, in mammals. This challenge was addressed in our © 2017 Society for Reproduction and Fertility This paper is part of an Anniversary Issue celebrating 30 Years of Interferon-Tau. ISSN 1470–1626 (paper) 1741–7899 (online) The Guest Editor for this section was Professor R Michael Roberts. DOI: 10.1530/REP-17-0257 Downloaded from Bioscientifica.com at 09/27/2021 05:06:35PM Online version via www.reproduction-online.org via free access 10.1530/REP-17-0257 F12 F W Bazer and W W Thatcher laboratories at the University of Florida through research (Moor & Rowson 1966a,b, Rowson & Moor 1967, with pigs, sheep and cows. Moor 1968). They also found that a blastocyst must be transferred into the uterine horn ipsilateral to the ovary bearing a CL by Day 12 or Day 13 of the oestrous cycle Pregnancy recognition signaling in pigs for establishment of a successful pregnancy. This was Research on proteins in uterine secretions, their confirmed by a study in which they found that length endocrine regulation and their influence on embryonic of the oestrous cycle of ewes was only affected when survival in pigs (see Bazer 1975) led to research on conceptuses were flushed from the uterus on or after mechanisms for establishment and maintenance of Day 13 of pregnancy (Moor & Rowson 1966a, Moor pregnancy in pigs, sheep and cows. Studies of the et al. 1969). Martal (1979) and Ellinwood and coworkers oestrous cycle and pregnancy in pigs revealed that (1979) reported an antiluteolytic factor in homogenates PGF was released into the uterine venous system in of sheep conceptuses collected on Days 14–15, but a pulsatile manner during the period of luteolysis in not Days 21–25 of pregnancy and homogenates of Day cyclic, but not pregnant gilts (see Bazer & Thatcher 14 and Day 15 conceptuses extended CL lifespan and 1977). Furthermore, it was discovered that the CL of pigs inter-oestrous intervals when infused into the uterine were not responsive to luteolytic effects of PGF until lumen of cyclic ewes (Rowson & Moor 1967, Ellinwood about Day 14 of the oestrous cycle; therefore, PGF was et al. 1979, Martal et al. 1979). The antiluteolytic factor ineffective as a hormone to synchronize estrus in pigs in the conceptus homogenates was confirmed to be (see Bazer et al. 1982). inactivated by heat and proteases. Martal et al. (1979) Our research on early pregnancy in pigs revealed named the antiluteolytic factor trophoblastin. Thus, it that blastocysts hatch from the zona pellucida between was established that maternal recognition of pregnancy Days 6 and 7, expand to large spherical blastocysts by signaling in ewes involved a protein secreted by the Day 10, and transition to tubular and filamentous forms conceptus between Days 12 and 21 after onset of estrus by Day 12 (1 mm diameter × 200 mm length) and Day and mating. 15 (800–1000 mm in length) of gestation (Geisert et al. 1982a,b,c). It was later established that elongating pig conceptuses secrete oestrogens (Perry et al. 1973, Discovery of interferon tau as the pregnancy Fischer et al. 1985), which are the pregnancy recognition recognition signal in ruminants signal in pigs (Bazer & Thatcher 1977). The endocrine- Our research on the estrogen-dependent endocrine- exocrine theory for pregnancy recognition in pigs was exocrine theory of pregnancy recognition in pigs (Bazer reported by Bazer and Thatcher (1977). The theory of & Thatcher 1977) biased our thinking toward the concept pregnancy recognition signaling in pigs was based on of oestrogen being the pregnancy recognition signal in results indicating that oestrogens, acting alone or in other livestock species, e.g., sheep and cows. Therefore, concert with prolactin, change the direction of secretion we studied steroid metabolism by uterine endometria of PGF from uterine epithelia from an endocrine to and conceptuses from sheep and cows. Results of those an exocrine direction. PGF is released from uterine studies provided no evidence for conceptus-derived epithelia into the vasculature of the uterus (endocrine oestrogens being the antiluteolytic factor secreted by secretion) in a pulsatile manner between Days 15 and conceptuses from sheep or cow conceptuses during 16 of the oestrous cycle to induce luteal regression. the period of pregnancy recognition signaling (see Eley However, PGF is secreted by uterine epithelia into the et al. 1979). Therefore, we cultured sheep conceptuses uterine lumen (exocrine direction) of pregnant pigs in medium containing radiolabeled amino acids where it is sequestered and metabolized (see Bazer & and analyzed culture medium to detect radiolabeled Thatcher 1977). This theory was confirmed and modified proteins that were synthesized de novo. We were using (see Zeicik et al. 2011). this method to identify proteins synthesized de novo and secreted into culture medium by explants of pig Pregnancy recognition signaling in ewes endometria (see Basha et al. 1980) (see Fig. 1). Ovine conceptus conditioned culture medium Rowson and Moor (1967) provided the first evidence that was first subjected to Sephadex G200 gel filtration ovine
Load more

Recommended publications
  • The Influence of Progesterone on Bovine Uterine Fluid Energy
    www.nature.com/scientificreports OPEN The infuence of progesterone on bovine uterine fuid energy, nucleotide, vitamin, cofactor, Received: 5 February 2019 Accepted: 7 May 2019 peptide, and xenobiotic Published: xx xx xxxx composition during the conceptus elongation-initiation window Constantine A. Simintiras, José M. Sánchez, Michael McDonald & Patrick Lonergan Conceptus elongation coincides with one of the periods of greatest pregnancy loss in cattle and is characterized by rapid trophectoderm expansion, commencing ~ Day 13 of pregnancy, i.e. before maternal pregnancy recognition. The process has yet to be recapitulated in vitro and does not occur in the absence of uterine gland secretions in vivo. Moreover, conceptus elongation rates are positively correlated to systemic progesterone in maternal circulation. It is, therefore, a maternally-driven and progesterone-correlated developmental phenomenon. This study aimed to comprehensively characterize the biochemical composition of the uterine luminal fuid on Days 12–14 – the elongation- initiation window – in heifers with normal vs. high progesterone, to identify molecules potentially involved in conceptus elongation initiation. Specifcally, nucleotide, vitamin, cofactor, xenobiotic, peptide, and energy metabolite profles of uterine luminal fuid were examined. A total of 59 metabolites were identifed, of which 6 and 3 displayed a respective progesterone and day efect, whereas 16 exhibited a day by progesterone interaction, of which 8 were nucleotide metabolites. Corresponding pathway enrichment
    [Show full text]
  • Actions of Interferon Tau During Maternal Recognition of Pregnancy Ações Do Interferon Tau Durante O Reconhecimento Materno Da Gestação
    Anais do XXIII Congresso Brasileiro de Reprodução Animal (CBRA-2019); Gramado, RS, 15 a 17 de maio de 2019. Actions of interferon tau during maternal recognition of pregnancy Ações do interferon tau durante o reconhecimento materno da gestação Alfredo Quites Antoniazzi1, £, Carolina dos Santos Amaral1, Alessandra Brid2 1BioRep – Laboratory of Biotechnology and Animal Reproduction, Federal University of Santa Maria, Santa Maria, RS, Brazil. 2Department of Veterinary Medicine, Faculty of Animal Sciences and Food Engineering, University of São Paulo, Pirassununga, SP, Brazil. Abstract Maternal recognition of pregnancy in ruminants is a physiological process that requires an interaction between the conceptus and the mother in order to avoid luteal regression. Studies on 60’s started to investigate the communication, and late on the 80’s it was identified a Type I interferon called interferon tau. In the 90’s the local action of interferon tau was described. It suppresses luteolytic pulses of prostaglandin F2 alpha inhibiting endometrial expression of estrogen and oxytocin receptors. Several studies presented the expression of interferon- stimulated genes on extrauterine tissues. After, the endocrine action of interferon tau was described. This study revealed a greater interferon bioactivity in the serum of uterine vein from pregnant ewes when compared to non- pregnant ewes. Following a series of experiments were preformed to better understand the endocrine action of interferon tau in several extrauteine tissues. This review presents the endocrine action of interferon tau during maternal recognition of pregnancy period in ruminants. Keywords: IFNT, pregnancy, endocrine, paracrine, interferon-stimulated genes, ruminants. Resumo O reconhecimento materno da gestação em ruminantes é um processo fisiológico que requer a interação entre o concepto e a mãe com o obejetivo de evitar a regressão luteal.
    [Show full text]
  • Interferon Receptor Signaling in Malignancy: a Network of Cellular Pathways Defining Biological Outcomes
    Published OnlineFirst September 12, 2014; DOI: 10.1158/1541-7786.MCR-14-0450 Molecular Cancer Review Research Interferon Receptor Signaling in Malignancy: A Network of Cellular Pathways Defining Biological Outcomes Eleanor N. Fish1 and Leonidas C. Platanias2 Abstract IFNs are cytokines with important antiproliferative activity and exhibit key roles in immune surveillance against malignancies. Early work initiated over three decades ago led to the discovery of IFN receptor activated Jak–Stat pathways and provided important insights into mechanisms for transcriptional activation of IFN- stimulated genes (ISG) that mediate IFN biologic responses. Since then, additional evidence has established critical roles for other receptor-activated signaling pathways in the induction of IFN activities. These include MAPK pathways, mTOR cascades, and PKC pathways. In addition, specific miRNAs appear to play a significant role in the regulation of IFN signaling responses. This review focuses on the emerging evidence for a model in which IFNs share signaling elements and pathways with growth factors and tumorigenic signals but engage them in a distinctive manner to mediate antiproliferative and antiviral responses. Mol Cancer Res; 12(12); 1691–703. Ó2014 AACR. Introduction as aplastic anemia (6). There is also recent evidence for Because of their antineoplastic, antiviral, and immuno- opposing actions of distinct IFN subtypes in the patho- modulatory properties, recombinant IFNs have been used physiology of certain diseases. For instance, a recent study extensively in the treatment of various diseases in humans demonstrated that there is an inverse association between (1). IFNs have clinical activity against several malignancies IFNb and IFNg gene expression in human leprosy, con- and are actively used in the treatment of solid tumors such sistent with opposing functions between type I and II as malignant melanoma and renal cell carcinoma; and IFNs in the pathophysiology of this disease (7).
    [Show full text]
  • Interferon-Tau Exerts Direct Prosurvival and Antiapoptotic
    www.nature.com/scientificreports OPEN Interferon-Tau Exerts Direct Prosurvival and Antiapoptotic Actions in Luteinized Bovine Received: 13 May 2019 Accepted: 23 September 2019 Granulosa Cells Published: xx xx xxxx Raghavendra Basavaraja1, Senasige Thilina Madusanka1, Jessica N. Drum 2, Ketan Shrestha1, Svetlana Farberov1, Milo C. Wiltbank3, Roberto Sartori2 & Rina Meidan 1 Interferon-tau (IFNT), serves as a signal to maintain the corpus luteum (CL) during early pregnancy in domestic ruminants. We investigated here whether IFNT directly afects the function of luteinized bovine granulosa cells (LGCs), a model for large-luteal cells. Recombinant ovine IFNT (roIFNT) induced the IFN-stimulated genes (ISGs; MX2, ISG15, and OAS1Y). IFNT induced a rapid and transient (15– 45 min) phosphorylation of STAT1, while total STAT1 protein was higher only after 24 h. IFNT treatment elevated viable LGCs numbers and decreased dead/apoptotic cell counts. Consistent with these efects on cell viability, IFNT upregulated cell survival proteins (MCL1, BCL-xL, and XIAP) and reduced the levels of gamma-H2AX, cleaved caspase-3, and thrombospondin-2 (THBS2) implicated in apoptosis. Notably, IFNT reversed the actions of THBS1 on cell viability, XIAP, and cleaved caspase-3. Furthermore, roIFNT stimulated proangiogenic genes, including FGF2, PDGFB, and PDGFAR. Corroborating the in vitro observations, CL collected from day 18 pregnant cows comprised higher ISGs together with elevated FGF2, PDGFB, and XIAP, compared with CL derived from day 18 cyclic cows. This study reveals that IFNT activates diverse pathways in LGCs, promoting survival and blood vessel stabilization while suppressing cell death signals. These mechanisms might contribute to CL maintenance during early pregnancy.
    [Show full text]
  • Early Pregnancy Induces Expression of STAT1, OAS1 and CXCL10 in Ovine Spleen
    animals Article Early Pregnancy Induces Expression of STAT1, OAS1 and CXCL10 in Ovine Spleen Yujiao Wang y, Xu Han y, Leying Zhang y, Nan Cao, Lidong Cao and Ling Yang * Department of Animal Science, College of Life Sciences and Food Engineering, Hebei University of Engineering, Handan 056021, China; [email protected] (Y.W.); [email protected] (X.H.); [email protected] (L.Z.); [email protected] (N.C.); [email protected] (L.C.) * Correspondence: [email protected] These authors contributed equally to this work. y Received: 20 September 2019; Accepted: 26 October 2019; Published: 30 October 2019 Simple Summary: Interferon-tau is a maternal recognition factor in ruminants, and spleen plays an essential role in regulating innate and adaptive immune responses. We found that interferon-tau derived from conceptus induces expression of STAT1, OAS1, and CXCL10 in ovine maternal spleen, which may be helpful for maternal immune regulation. Abstract: Interferon-tau is a maternal recognition factor in ruminant species, and spleen plays an essential role in regulating innate and adaptive immune responses. However, it is not fully understood that early pregnancy induces expression of interferon stimulated genes (ISGs) in the spleen during early pregnancy in ewes. In this study, spleens were collected from ewes at day 16 of the estrous cycle, and on days 13, 16, and 25 of gestation (n = 6 for each group), and RT-qPCR, western blot and immunohistochemistry analysis were used to detect the expression of signal transducer and activator of transcription 1 (STAT1), 20,50-oligoadenylate synthetase 1 (OAS1), myxovirusresistance protein 1 (Mx1) and C-X-C motif chemokine 10 (CXCL10).
    [Show full text]
  • Upregulation of Interferon-Stimulated Genes and Interleukin-10
    Journal of Reproduction and Development, Vol. 58, No 1, 2012 —Original Article— Upregulation of Interferon-stimulated Genes and Interleukin-10 in Peripheral Blood Immune Cells During Early Pregnancy in Dairy Cows Koumei SHIRAsuNA1), Haruka MATsumOTO1), Eiji KOBAYASHI1), Akane NiTTA1), Shingo HANedA2), Motozumi MATsui2), Chiho KAWASHimA3), Katsuya KidA3), Takashi SHimiZU1) and Akio MIYAMOTO1) 1)Graduate School of Animal and Food Hygiene, Obihiro University of Agriculture and Veterinary Medicine, Obihiro 080-8555, Japan 2)Department of Clinical Veterinary Science, Obihiro University of Agriculture and Veterinary Medicine, Obihiro 080-8555, Japan 3)Field Center of Animal Science and Agriculture, Obihiro University of Agriculture and Veterinary Medicine, Obihiro 080-8555, Japan Abstract. In cows, interferon-tau (IFNT) regulates maternal recognition around days 15–19 after artificial insemination (AI). The present study hypothesized that if key target genes of IFNT are clearly upregulated in earlier stages of pregnancy, these genes could be use as indices of future pregnancy in cows. Therefore, we determined the expression of these genes in peripheral blood mononuclear leukocytes (PBMCs) and polymorphonuclear granulocytes (PMNs) during the maternal recognition period (MRP). Twenty multiparous Holstein cows were subjected to AI on day 0 and categorized into the following groups: pregnancy (Preg, n = 9), embryonic death (ED, n = 5) and non-pregnancy (NP, n = 6). Progesterone levels in the Preg group were higher than those in the NP group on days 12–21. ISG15 and OAS-1 (IFN-stimulated genes: ISGs) mRNA in PBMCs on day 8 was higher in the Preg group than in the NP group, and these mRNAs in PMNs was higher in the Preg group on day 5 than in the NP and ED groups.
    [Show full text]
  • Peritoneal Environment, Cytokines and Angiogenesis in The
    REPRODUCTIONRESEARCH Possible role of interferon tau on the bovine corpus luteum and neutrophils during the early pregnancy Koumei Shirasuna, Haruka Matsumoto1, Shuichi Matsuyama2, Koji Kimura3, Heinrich Bollwein4 and Akio Miyamoto1 Department of Animal Science, Tokyo University of Agriculture, Atsugi 243-0034, Japan, 1Graduate School of Animal and Food Hygiene, Obihiro University of Agriculture and Veterinary Medicine, Obihiro 080-8555, Japan, 2Animal Feeding and Management Research Division, NARO Institute of Livestock and Grassland Science, Nasushiobara 329-2793, Japan, 3Graduate School of Environmental and Life Science, Okayama University, Okayama 700-8530, Japan and 4Clinic for Reproduction Medicine, University of Zu¨rich, Zurich, Switzerland Correspondence should be addressed to A Miyamoto; Email: [email protected] Abstract When pregnancy is established, interferon tau (IFNT), a well-known pregnancy recognition signal in ruminants, is secreted by embryonic trophoblast cells and acts within the uterus to prepare for pregnancy. IFNT acts as an endocrine factor on the corpus luteum (CL) to induce refractory ability against the luteolytic action of PGF2a. Hypothesising that IFNT may influence not only the uterine environment but also the CL in cows via local or peripheral circulation, we investigated qualitative changes in the CL of pregnant cows during the maternal recognition period (day 16) and the CL of non-pregnant cows. The CL of pregnant animals had a higher number of neutrophils, and the expression of interleukin 8 (IL8) mRNA and its protein was higher as well as compared with the CL of non-pregnant animals. Although IFNT did not affect progesterone (P4) secretion and neutrophil migration directly, it stimulated IL8 mRNA expression on luteal cells (LCs), influencing the neutrophils, resulting in the increased migration of IFNT-activated neutrophils.
    [Show full text]
  • Interferons Using ALZET Osmotic Pumps
    ALZET® Bibliography References on the Administration of Interferons Using ALZET Osmotic Pumps 1. Alpha Q7344: R. Gutierrez Jauregui, et al. IL-1beta Promotes Staphylococcus aureus Biofilms on Implants in vivo. Front Immunol 2019;10(1082 Agents: Interleukin-1 beta; Interleukin-6; Interleukin-10; Interleukin-12; Interleukin-17; Interleukin-23; Interferon, gamma; Tumor Necrosis Factor, alpha; Interleukin-1 beta, anti; Transforming Growth Factor-B1, anti Vehicle: PBS; Route: SC; Species: Mice; Pump: 1007D; Duration: 10 Days; ALZET Comments: Dose (IL-1b (83μg/ml); IL-6 (83μg/ml); IL-10 (166μg/ml); IL-12 (83μg/ml); IL-17 (125μg/ml); IL-23 (166μg/ml); IFNg (83μg/ml); TNFa (166μg/ml); anti-TGF-b1 (166μg/ml); anti-IL-1b (150μg/ml)); Controls received mp w/ vehicle; animal info (Eight- to twelve-week-old female C57BL/6 mice); Immunology (“evaluate the suitability of osmotic pumps as a model for biofilms in implant associated infections, we implanted osmotic pumps pre-colonized with bioluminescent Staphylococcus aureus”); Q1983: Y. Yuan, et al. Role of microRNA-15a in autoantibody production in interferon-augmented murine model of lupus. MOLECULAR IMMUNOLOGY 2012;52(2):61-70 Agents: Interferon, alpha; interferon, gamma Vehicle: PBS; BSA; Route: SC; Species: Mice; Pump: 2006; Duration: 16 weeks; ALZET Comments: Animal info (13 wks old, female, B/W); pumps replaced after 8 weeks; long-term study; stability verified after 8 weeks; "residue IFNs from the pumps at the end of treatment were tested on IFN and IFN responsive cell lines and demonstrated that the in vivo conditions in the pump did not affect bioactivity of both IFNs (data not shown)" pg 63 P9300: A.
    [Show full text]
  • Early Pregnancy-Induced Transcripts in Peripheral Blood Immune Cells In
    www.nature.com/scientificreports OPEN Early pregnancy‑induced transcripts in peripheral blood immune cells in Bos indicus heifers Cecilia Constantino Rocha1, Sónia Cristina da Silva Andrade2, Gabriela Dalmaso de Melo1, Igor Garcia Motta1, Luiz Lehmann Coutinho3, Angela Maria Gonella‑Diaza4, Mario Binelli5 & Guilherme Pugliesi1* Immune cells play a central role in early pregnancy establishment in cattle. We aimed to: (1) discover novel early-pregnancy-induced genes in peripheral blood mononuclear cells (PBMC); and (2) characterize the temporal pattern of early‑pregnancy‑induced transcription of select genes in PBMC and peripheral blood polymorphonuclear cells (PMN). Beef heifers were artifcially inseminated on D0 and pregnancies were diagnosed on D28. On D10, 14, 16, 18, and 20, blood was collected for isolation of PBMC and PMN from heifers that were retrospectively classifed as pregnant (P) or non-pregnant (NP). PBMC samples from D18 were submitted to RNAseq and 220 genes were diferentially expressed between pregnant (P) and non-pregnant (NP) heifers. The temporal abundance of 20 transcripts was compared between P and NP, both in PBMC and PMN. In PBMC, pregnancy stimulated transcription of IFI6, RSAD2, IFI44, IFITM2, CLEC3B, OAS2, TNFSF13B, DMKN and LGALS3BP as early as D18. Expression of IFI44, RSAD2, OAS2, LGALS3BP, IFI6 and C1R in PMN was stimulated in the P group from D18. The novel early-pregnancy induced genes discovered in beef heifers will allow both the understanding of the role of immune cells during the pre‑attachment period and the development of technologies to detect early pregnancies in beef cattle. In cattle, pregnancy success depends on the maintenance of a functional corpus luteum (CL) beyond the time of luteolysis, which normally occurs between days 15 and 18 of the estrous cycle 1,2.
    [Show full text]
  • Interferon Tau in the Ovine Uterus Gwonhwa Song*, Jae Yong Han*, Thomas E
    J. Anim. Sci. & Technol. 51(6) 471~484, 2009 Interferon Tau in the Ovine Uterus Gwonhwa Song*, Jae Yong Han*, Thomas E. Spencer** and Fuller W. Bazer*, ** WCU Biomodulation Major, Department of Agricultural Biotechnology, and Research Institute for Agriculture and Life Sciences, Seoul National University, Korea*, Department of Animal Science, Center for Animal Biotechnology and Genomics, Texas A&M University, 442 Kleberg Center, 2471 TAMU, College Station, Texas 77843-2471, USA ** ABSTRACT The peri-implantation period in mammals is critical with respect to survival of the conceptus (embryo/fetus and associated extraembryonic membranes) and establishment of pregnancy. During this period of pregnancy, reciprocal communication between ovary, conceptus, and endometrium is required for successful implantation and placentation. At this time, interferon tau (IFNT) is synthesized and secreted by the mononuclear trophectodermal cells of the conceptus between days 10 and 21~25. The actions of IFNT to signal pregnancy recognition and induce or increase expression of IFNT-stimulated genes (ISGs), such as ISG15 and OAS, are mediated by the Type I IFN signal transduction pathway. This article reviews the history, signaling pathways of IFNT and the uterine expression of several IFNT-stimulated genes during the peri-implantation period. Collectively, these newly identified genes are believed to be critical to unraveling the mechanism(s) of reciprocal fetal-maternal interactions required for successful implantation and pregnancy. (Key words : Interferon tau, Progesterone, Sheep, Uterus, Implantation) INTRODUCTION Spencer and Bazer, 1995). Thus, oxytocin from the posterior pituitary and/or corpus luteum (CL) can then induce release of In eutherian mammals, including sheep, implantation of the luteolytic pulses of PGF on days 15 and 16 (Hooper et al., blastocyst is a most important developmental event associated 1986).
    [Show full text]
  • Gene Expression Profiles of Bovine Caruncular and Intercaruncular
    Gene expression profiles of bovine caruncular and intercaruncular endometrium at implantation Nadera Mansouri-Atiia, Julie Aubert, Pierrette Reinaud, Corinne Giraud-Delville, Geraldine Taghouti, Laurent Galio, Robin, E. Everts, Severine Degrelle, Christophe Richard, Isabelle Hue, et al. To cite this version: Nadera Mansouri-Atiia, Julie Aubert, Pierrette Reinaud, Corinne Giraud-Delville, Geraldine Taghouti, et al.. Gene expression profiles of bovine caruncular and intercaruncular endometrium at implantation. Physiological Genomics, American Physiological Society, 2009, 39 (1), pp.14-27. 10.1152/physiolge- nomics.90404.2008. hal-01197513 HAL Id: hal-01197513 https://hal.archives-ouvertes.fr/hal-01197513 Submitted on 31 May 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Nadéra Mansouri-Attia, Julie Aubert, Pierrette Reinaud, Corinne Giraud-Delville, Géraldine Taghouti, Laurent Galio, Robin E. Everts, Séverine Degrelle, Christophe Richard, Isabelle Hue, Xiangzhong Yang, X. Cindy Tian, Harris A. Lewin, Jean-Paul Renard and Olivier Sandra Physiol
    [Show full text]
  • BCL2L15 Depletion Inhibits Endometrial Receptivity Via the STAT1 Signaling Pathway
    G C A T T A C G G C A T genes Article BCL2L15 Depletion Inhibits Endometrial Receptivity via the STAT1 Signaling Pathway Diqi Yang, Ai Liu, Yanqin Wu, Bin Li, Sha Nan, Ruiling Yin, Hongmei Zhu, Jianguo Chen, Yi Ding and Mingxing Ding * College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; [email protected] (D.Y.); [email protected] (A.L.); [email protected] (Y.W.); [email protected] (B.L.); [email protected] (S.N.); [email protected] (R.Y.); [email protected] (H.Z.); [email protected] (J.C.); [email protected] (Y.D.) * Correspondence: [email protected] Received: 8 June 2020; Accepted: 16 July 2020; Published: 17 July 2020 Abstract: In domestic ruminants, endometrial receptivity is critical for a successful pregnancy and economic efficiency. Although the endometrium undergoes major cellular changes during peri-implantation, the precise mechanisms regulating goat endometrial receptivity remain unknown. In this study, we investigated the functional roles and signal transduction of the B-cell lymphoma 2 (Bcl-2)-like protein 15 (BCL2L15) in the regulation of endometrial receptivity in vitro. Our results showed that BCL2L15 was up-regulated in goat endometrial epithelial cells (EECs) under progesterone (P4), estradiol (E2), and interferon-tau (IFN-τ) treatments. Our knockdown of BCL2L15 by specific shRNA that significantly hampered endometrial receptivity. In the absence of BCL2L15, the signal transducer and activator of transcription (STAT)1 and STAT3 pathway were activated. Additionally, pretreatment with the STAT1 inhibitor, fludarabine, restored the effect of silencing BCL2L15 on the endometrial receptivity, but not the STAT3 inhibitor Stattic.
    [Show full text]